Figure 3.

The role of Dot1 in telomeric silencing. Telomeric DNA silencing in Saccharomyces cerevisiae is established by the binding of the Sir proteins, including Sir3, to chromatin. Competition between H3K79 methylation by Dot1 and Sir protein binding regulates heterochromatin formation at telomeres. Methylation of H3K79 prevents the binding of Sir3 and therefore disrupts telomeric silencing. Conversely, binding of Sir3 to unmethylated H3K79 prevents the interaction of Dot1 with chromatin by outcompeting Dot1 for binding to a basic patch on histone H4 which is essential for Dot1 recruitment and H3K79 methylation.